Recent studies on the frequency-dependent block of excitability in nerve by local anesthetics have established a new understanding of how these agents work at the molecular level. Since these new findings may relate to the anti-arrhythmic effectiveness of local anesthetics in the heart, proposed are extensive new investigations and tests of these recently developed concepts in cardiac muscle. Many different local anesthetics, as well as several other types of antiarrhythmic agents, will be tested for use-dependent enhancement of sodium conductance block, as measured by the decrement of maximum upstroke velocity in cardiac action potentials. Recovery from this use-dependent increase in block also will be studied in detail, especially relative to the effect of membrane potential and drug concentration of this recovery process. The proposed experiments will concern propagation of rhythmic impulses between pacemaker and atrial muscle and arrhythmic trains of impulses within atrial muscle. Subsidiary studies on ventricular muscle also are planned. The integrity of the autonomic system of heart rate control will be assessed also during exposure to these drugs.